Trypanosoma cruzi, the protozoan that causes Chagas disease, is a major cause of morbidity and mortality in South and Central America, primarily among poor persons. The current international effort to eliminate Chagas disease as a public health problem has two goals: to prevent transmission of the parasite to human beings and to identify and treat the millions of people who are already infected in order to prevent life-threatening sequelae. The last decade has provided a series of potential new tools (specifically, advanced immunology, proteomics, molecular biology / molecular epidemiology, genomics, spatial analysis, simulation models) that have only begun to be applied for the diagnosis, epidemiology and control of parasitic diseases. The main theme of the Peru TMRC Program is to apply new tools and information in a concerted manner to develop novel diagnostic and control methods for Chagas disease which could be applied elsewhere. Two Research Projects and Three Cores compose the Program. The overall aim for Research Project 1 is to compare Chagas transmission patterns in rural and urban communities, using ecologic, epidemiologic, qualitative and spatial analysis methods as well as high-resolution molecular characterization of Trypanosoma cruzi and Triatoma infestans in order to develop strategies for control, and the Overall Aim of Research Project 2 is to address the central diagnostic dilemmas of Chagas disease-efficient population screening, timely identification of antitrypanosomal treatment failures, and early detection of those most likely to progress to severe disease - through optimization of existing assays and development of novel diagnostic tools using genomic and proteomic approaches. The above research components of this application encompass several closely connected studies that focus on the twin goals of the global elimination effort: Improved control through: 1 - A rigorous analysis of the ecology and epidemiology of human Chagas disease and its vector in contrasting rural and peri-urban sites with ongoing vectorial T. cruzi transmission;and 2 - Improved guidance for residual insecticide application and post-applicationsurveillance for re-infestation, especially in peri-urban settings;and Improved tools for diagnosis and treatment: 3 - Novel screening strategies to identify T. crazy-infected children;and 4 -New assays and improved use of existing assays for more effective diagnosis of chronic and congenital infection, and to identify early treatment failures after antitrypanosomal treatment. An administrative core (Core A) and two Scientific Cores (Core B - Immunology / Molecular Biology and Core C- Epidemiology / GIS / Data Management) form the structure of the Program. PROJECT 1: The Ecology and Epidemiology of Chagas Disease in Urban and Rural Communities in Southern Peru (Gonzalez, A.) PROJECT 1 DESCRIPTION (provided by applicant): The elimination of T. infestans from the remaining infested Chagas-disease endemic areas of the Southern Cone presents difficult challenges because of limited resources, atypical ecology, and biological and operational obstacles to vector control. Southern Peru is a prime example: delays in implementing control measures, massive rural to urban migration, and densely situated houses built on and of volcanic rock have resulted in complex urban transmission cycles. Innovative strategies are needed to ensure the success of vector control in Peru;failure to do so puts neighboring countries at risk for re-infestation by the vector and jeopardizes the entire Southern Cone Initiative. Recent introduction of vectors and parasite into the city of Arequipa itself allows analysis of the trend of urbanization of Chagas disease transmission and identification of modifications necessary to eliminate the vector from the urban environment. We plan to use modern molecular tools and spatial analysis to identify similarities that link rural and urban foci to understand how the ecology and epidemiology of the urban and periurban environment differs from that in traditional rural endemic zones. The overall aim of Research Project 1 is to develop strategies for control of Chagas disease based on a comparative analysis of transmission patterns in rural and urban communities, using ecologic, epidemiologic, qualitative and spatial methods in concert with high resolution molecular characterization of Trypanosoma cruzi and Triatoma infestans. The methods will include a rigorous analysis of the ecology and epidemiology of human Chagas disease and its vector in contrasting rural and peri-urban sites with ongoing vectorial T. cruzi transmission, using assessment of human, animal, and vector T. cruzi infections rates and spatial patterns, and a qualitative study of human migration and animal husbandry patterns. Studies of vector reinfestation utilizing population genetics analyses of recently developed T. infestans microsatellite markers and dynamic risk maps of reinfestation risk will provide improved guidance for residual insecticide application and post application surveillance for re-infestation, especially in peri-urban settings. Finally we will use georeferenced data on infestation and T. cruzi infected vectors to improve the efficiency of targeted serologic screening to identify T.cruzi infected children. The data from this Project will have immediate applicability for the regional Chagas disease control program in Arequipa and in other endemic areas.